Treatment of Alport mice with the small molecule inhibitor for FAK, TAE226, blocks FAK activation, significantly reduces glomerular expression of MMP-9, -10, and -12, and ameliorates proteinuria and blood urea nitrogen levels.

<p>129 Sv/J autosomal Alport mice were treated with TAE226 from 2 to 7 weeks of age. Panels A–F show that while pFAK³⁹⁷ immunostaining is present in podocytes adjacent to laminin α2-immunopositive basement membranes in vehicle treated mice, it is absent in mice treated with TAE226, indicating effective blockade. Real time qRT-PCR analysis of glomerular RNA in panel G shows significant reduction in expression of MMP-9, MMP-10, and MMP-12 in TAE226 treated mice relative to those given vehicle. Panel H and I show significant amelioration of proteinuria and BUN in treated mice, indicative of improved glomerular function. Scale bar = 15 µm.